rs872106

chr10-97476460-C-Gchr10-97476460-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022362.5(MMS19):c.684+223G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,144 control chromosomes in the GnomAD database, including 4,207 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4207 hom., cov: 32)
• Consequence: MMS19 NM_022362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

Genes affected

MMS19 (HGNC:13824): (MMS19 homolog, cytosolic iron-sulfur assembly component) Enables estrogen receptor binding activity and transcription coactivator activity. Involved in several processes, including iron-sulfur cluster assembly; positive regulation of nucleobase-containing compound metabolic process; and protein maturation by iron-sulfur cluster transfer. Located in cytosol; nucleoplasm; and spindle. Part of CIA complex and MMXD complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMS19	NM_022362.5	c.684+223G>C		intron_variant		ENST00000438925.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMS19	ENST00000438925.7	c.684+223G>C		intron_variant		1	NM_022362.5	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34381 AN: 152026 Hom.: 4206 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0356

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.210

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 34404 AN: 152144 Hom.: 4207 Cov.: 32 AF XY: 0.226 AC XY: 16823 AN XY: 74370

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0358

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.209

Alfa AF: 0.163 Hom.: 348

Bravo AF: 0.212

Asia WGS AF: 0.138 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.7
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs872106; hg19: chr10-99236217;